TY - JOUR
T1 - Ion channel activity of the BH3 only Bcl-2 family member, BID
AU - Schendel, Sharon L.
AU - Azimov, Rustam
AU - Pawłowski, Krzysztof
AU - Godzik, Adam
AU - Kagan, Bruce L.
AU - Reed, John C.
PY - 1999/7/30
Y1 - 1999/7/30
N2 - BID is a member of the BH3-only subgroup of Bcl-2 family proteins that displays pro-apoptotic activity. The NH2-terminal region of BID contains a caspase-8 (Casp-8) cleavage site and the cleaved form of BID translocates to mitochondrial membranes where it is a potent inducer of cytochrome c release. Secondary structure and fold predictions suggest that BID has a high degree of α-helical content and structural similarity to Bcl-X(L), which itself is highly similar to bacterial pore-forming toxins. Moreover, circular dichroism analysis confirmed a high α-helical content of BID. Amino-terminal truncated BIDA1-55, mimicking the Casp-8-cleaved molecule, formed channels in planar bilayers at neutral pH and in liposomes at acidic pH. In contrast, full- length BID displayed channel activity only at nonphysiological pH 4.0 (but not at neutral pH) in planar bilayers and failed to form channels in liposomes even under acidic conditions. On a single channel level, BIDA1-55 channels were voltage-gated and exhibited multiconductance behavior at neutral pH. When full-length BID was cleaved by Casp-8, it too demonstrated channel activity similar to that seen with BIDA1-55. Thus, BID appears to share structural and functional similarity with other Bcl-2 family proteins known to have channel-forming activity, but its activity exhibits a novel form of activation: proteolytic cleavage.
AB - BID is a member of the BH3-only subgroup of Bcl-2 family proteins that displays pro-apoptotic activity. The NH2-terminal region of BID contains a caspase-8 (Casp-8) cleavage site and the cleaved form of BID translocates to mitochondrial membranes where it is a potent inducer of cytochrome c release. Secondary structure and fold predictions suggest that BID has a high degree of α-helical content and structural similarity to Bcl-X(L), which itself is highly similar to bacterial pore-forming toxins. Moreover, circular dichroism analysis confirmed a high α-helical content of BID. Amino-terminal truncated BIDA1-55, mimicking the Casp-8-cleaved molecule, formed channels in planar bilayers at neutral pH and in liposomes at acidic pH. In contrast, full- length BID displayed channel activity only at nonphysiological pH 4.0 (but not at neutral pH) in planar bilayers and failed to form channels in liposomes even under acidic conditions. On a single channel level, BIDA1-55 channels were voltage-gated and exhibited multiconductance behavior at neutral pH. When full-length BID was cleaved by Casp-8, it too demonstrated channel activity similar to that seen with BIDA1-55. Thus, BID appears to share structural and functional similarity with other Bcl-2 family proteins known to have channel-forming activity, but its activity exhibits a novel form of activation: proteolytic cleavage.
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U2 - 10.1074/jbc.274.31.21932
DO - 10.1074/jbc.274.31.21932
M3 - Article
C2 - 10419515
AN - SCOPUS:0033618409
SN - 0021-9258
VL - 274
SP - 21932
EP - 21936
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 31
ER -